Pulmonary artery banding in a kitten with a partial atrioventricular septal defect.

A 9-month-old kitten with increased resting respiratory rate and exercise intolerance was diagnosed with a congenital partial atrioventricular septal defect causing pulmonary over circulation and presumed pulmonary hypertension based on echocardiogram. Invasive pressure measurements and contrast angiography confirmed this diagnosis. The cat underwent pulmonary artery banding under general anesthesia. Findings of echocardiogram 10 days postoperatively suggested reduced left-to-right shunt volume. Echocardiographic findings were static 4 months postoperatively.

Feline visceral hemangiosarcoma.

BACKGROUND: Feline visceral hemangiosarcoma (HSA) is an uncommon tumor, and the clinical progression and outcome are rarely reported. HYPOTHESIS: The prognosis of feline visceral HSA is poor because of severe clinical signs, anemia, and a high rate of metastasis. ANIMALS: The medical records of 26 client-owned cats with visceral HSA were reviewed. METHODS: Multi-institutional retrospective study. RESULTS: The most common historical findings and clinical signs included lethargy, anorexia, respiratory difficulty, collapse, and vocalizing. Eighty-two percent of cats were anemic, and aspartate transaminase was increased in 53% of the study population. Metastatic lung disease was noted in 33% of affected cats. In 75% of the cats, abdominal ultrasonography identified a specific location of HSA. However, ultrasound identification of all multifocal lesions was successful only in 3/9 cats (33%). Tumor location was identified in the following organs: liver (35%), small intestine (31%), large intestine (31%), abdominal lymph node (31%), mesentery (27%), spleen (23%), lung (19%), omentum (12%), brain (8%), pancreas (8%), and diaphragm (8%). Multifocal HSA was noted in 77% of cats. Three cats received adjuvant chemotherapy (doxorubicin). Seventy-one percent of euthanized cats were euthanized within 1 day of diagnosis. The median survival time of the remaining cats (n = 6) was 77 days (range, 23-296 days). CONCLUSION AND CLINICAL IMPORTANCE: Feline visceral HSA is most often multifocal at the time of diagnosis. The prognosis appears poor, and the number of cats receiving chemotherapy is low.

Patient satisfaction with an injection device for multiple sclerosis treatment.

OBJECTIVES: To develop a measure of treatment satisfaction assessing attributes specific to injected interferon-beta-1a (IFN-beta-1a) for multiple sclerosis (MS), and to test pain and instrument sensitivity to change among patients changing injection devices. MATERIALS AND METHODS: The MS Treatment Concerns Questionnaire (MSTCQ) was developed and tested with pain assessments before and 3 months after patients changed devices from Rebiject to Rebiject II. RESULTS: The MSTCQ was organized with two domains: Injection System Satisfaction and Side Effects (three subscales: Injection Site Reactions, Global Satisfaction, and Flu-Like Symptoms). Significant improvements (P = 0.002 to P < 0.001) occurred with the new injection device in all MSTCQ subscales (except Flu-Like Symptoms), and all pain measures (P < 0.0001). Clinically meaningful improvement was demonstrated in all scales, except Flu-Like Symptoms, by effect sizes (0.23-0.59). CONCLUSIONS: These statistically significant and clinically meaningful improvements in MSTCQ and pain measures show the value of technologically advanced devices in domains of concern to patients.

Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning.

Recent studies suggest that ischemia activates Src and members of the mitogen-activated protein (MAP) kinase superfamily and their downstream effectors, including big MAP kinase 1 (BMK1) and p90 ribosomal S6 kinase (p90RSK). It has also been reported that adenosine is released during ischemia and involved in triggering the protective mechanism of ischemic preconditioning. To assess the roles of Src and adenosine in ischemia-induced MAP kinases activation, we utilized the Src inhibitor PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (SPT) in perfused guinea pig hearts. PP2 (1 microm) inhibited ischemia-induced Src, BMK1 and JNK activation but not JAK2 and p38 activation. SPT inhibited ischemia-mediated p38 and JNK activation. These results demonstrate that Src family kinase and adenosine regulate MAP kinases by parallel pathways. Preconditioning significantly improved both recovery of developed pressure and dp/dt in isolated guinea pig hearts. Since the protective effect of preconditioning was blocked by PP2 (1 microm) and SPT (50 microm), we next investigated the regulation of Src, MAP kinases and p90RSK during preconditioning. The activity and time course of ERK1/2 was not changed, but p90RSK activation by reperfusion was completely inhibited by preconditioning. In contrast, the activation by ischemia of Src, BMK1, p38 and JNK was significantly faster in preconditioned hearts. Maximal BMK1 activation by ischemia was also significantly enhanced by preconditioning. These data suggest important roles for Src family kinases and adenosine in mediating preconditioning, and suggest specific roles for individual MAP kinases in preconditioning.

p160 Bcr mediates platelet-derived growth factor activation of extracellular signal-regulated kinase in vascular smooth muscle cells.

BACKGROUND: The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene, which is causative for chronic myeloblastic leukemia. Because Bcr encodes a serine/threonine protein kinase, we studied its kinase activity and determined the role of Bcr in the PDGF signaling pathway to ERK1/2 activation and DNA synthesis in rat aortic smooth muscle cells (RASMCs). METHODS AND RESULTS: In RASMCs, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity, with a maximum at 1 minute. Because phosphatidylinositol 3'-kinase (PI3-K) is essential for Bcr/Abl leukemogenesis, we evaluated the role of mouse PDGF-beta-receptor binding sites for PI3-K (Y708, Y719) and for phospholipase C-gamma (Y977, Y989) in PDGF-mediated Bcr kinase activation. The mutant PDGF receptor Y708F/Y719F but not Y977F/Y989F showed significantly reduced Bcr kinase activity. To determine the role of Bcr in PDGF-mediated signal transduction events leading to ERK1/2 and its downstream Elk1 transcription activation, wild-type (WT) and kinase-negative (KN) Bcr were transiently expressed in RASMCs. Bcr WT enhanced, whereas Bcr KN inhibited, PDGF-stimulated ERK1/2 and Elk1 transcriptional activity. Overexpression of Bcr also enhanced PDGF-induced Ras/Raf-1 activity and DNA synthesis, but this regulation is independent of the kinase activity of Bcr. Finally, we found that Bcr expression was increased in the neointimal layer after balloon injury of rat carotid artery. CONCLUSIONS: These results demonstrated the importance of Bcr in PDGF-mediated events, such as activation of Ras, Raf-1, ERK1/2, and Elk1, and stimulation of DNA synthesis.

Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.

Activation of members of the mitogen-activated protein (MAP) kinase family and their downstream effectors has been proposed to play a key role in the pathogenesis of cell survival, ischaemic preconditioning, cardiac hypertrophy and heart failure. This study investigated the responses of Src kinase and multiple MAP kinases during the transition from compensated pressure-overload hypertrophy to decompensated congestive heart failure. Extracellular signal-regulated protein kinase (ERK) 1/2, p38, and Src were activated by chronic pressure-overload and their activity was sustained for 8 weeks after aortic banding. In contrast, while p90 ribosomal S6 kinase (90RSK) and big MAP kinase 1 (BMK1) were activated in compensated hypertrophy, their activities were significantly decreased in hearts with heart failure. No changes were found in C-Jun NH2 terminal kinase (JNK) activity after aortic banding. These data suggest that differential activation of MAP kinase family members may contribute to the transition from compensated to decompensated hypertrophy. We also examined acute effects of mechanical stretch on the activation of these kinases in normal and hypertrophied hearts. In the isolated coronary-perfused heart, a balloon in the left ventricle was inflated to achieve minimum end-diastolic pressure of 25 mmHg for 10-20 min. In normal guinea pig hearts, stretch activated ERK1/2, p90RSK, p38, Src, and BMK1 but not JNK. However in hypertrophied hearts, further activation of these kinases was not observed by acute mechanical stretch. Mechanical stretch-induced activation of ERK1/2 and p38 kinase in normal hearts was attenuated significantly by a protein kinase C inhibitor, chelerythrine. We demonstrate that ERK1/2, p90RSK, p38, Src, and BMK1 are activated by chronic pressure-overload and by acute mechanical stretch. These data suggest that Src, BMK1 and p90RSK play a role as novel signal transduction pathways leading to cardiac hypertrophy. In addition, the differential inhibition of p90RSK and BMK1 in hearts with congestive heart failure suggests the specific role of these two kinases to maintain cardiac function under chronic pressure-overload.

Intrusion, avoidance, and psychological distress among individuals with cancer.

OBJECTIVE: The goal of the study was to examine the utility of Creamer's cognitive processing theory of trauma in a sample of individuals undergoing treatment for cancer. This theory proposes that avoidance is a maladaptive strategy of dealing with intrusive thoughts about a traumatic experience and suggests that avoidance mediates the relation between intrusive thoughts and later psychological distress. The role of disease-related factors, specifically changes in physical impairment and disease stage, was also examined. METHODS: Patients (N = 189) undergoing treatment for cancer completed questionnaires at three time points, spaced 3 months apart. Intrusive thoughts, functional impairment, and psychological distress were assessed at Time 1, avoidance and functional impairment at Time 2, and psychological distress was assessed again at Time 3. The fit of the model was tested separately for patients with early-stage (stages 1 and 2) and late-stage (stages 3 and 4) disease. RESULTS: The mediational role for avoidance was supported among patients with advanced stages of cancer but not for patients with early-stage disease. Results were inconsistent with predictions about the role of physical impairment. Among individuals with late-stage cancer, changes in functional impairment were not predictive of greater avoidance, and impairment had a significant but weak effect on the change in distress. Among patients with early-stage cancer, a deterioration in physical impairment was associated with increases in avoidance, and deterioration in physical impairment increased distress. CONCLUSIONS: The results of this study were partially consistent with Creamer's cognitive processing theory. A moderating effect was found for disease stage on associations between intrusions, avoidance, physical impairment, and distress.

Bcr in vascular smooth muscle cells involvement of Ras and Raf-1 activation by Bcr.

Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene. In vascular smooth muscle cells, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity. The mutant PDGF receptor for PI3-K, but not for PLC-gamma binding sites, showed significantly reduced Bcr kinase activity. Bcr wild-type enhanced, whereas Bcr kinase negative form inhibited PDGF-stimulated ERK1/2 activity. A dominant negative Ras did not inhibit Bcr kinase activation, and overexpression of Bcr increased Ras/Raf-1 activity and DNA synthesis. These results demonstrated the importance of Bcr in PDGF-mediated events such as activation of Ras, Raf-1, and ERK1/2 and stimulation of DNA synthesis.

Effective use of botox for lateral canthal rhytids.

The authors discuss why Botox is their preferred nonsurgical treatment for lateral canthal rhytids, or crow's-feet. Three or 4 injections are spaced at 1.0- to 1.5-cm intervals beginning immediately beneath the lateral edge of the eyebrow and extending down to the lateral infraorbital rim. Complications are infrequent and can usually be avoided with the injection techniques described.

Single mothers in low-wage jobs: financial strain, parenting, and preschoolers' outcomes.

Using data from an ongoing study of 93 single Black mothers of preschoolers who had been welfare recipients, but were employed in low-wage jobs at baseline, this study tests a model of how maternal education, economic conditions (earnings and financial strain), and the availability of instrumental support influence maternal psychological functioning, parenting, and child development. Results indicate that maternal educational attainment was positively associated with earnings, which, together with instrumental support, were negatively associated with financial strain. Financial strain, in turn, was implicated in elevated levels of depressive symptoms, which were directly and negatively implicated in parenting quality. The quality of parenting was associated with children's behavior problems and preschool ability. Specifically, mothers with higher scores on the HOME scale, our measure of involved, supportive parenting, had children with fewer behavior problems and better preschool ability.

Perceived control, coping efficacy, and avoidance coping as mediators between spouses' unsupportive behaviors and cancer patients' psychological distress.

This study examined whether avoidance, coping efficacy, and perceived control mediate the effects of spouses' unsupportive behaviors on patient psychological distress among 191 married individuals enrolled in cancer treatment. Results of the structural equation analyses suggested that avoidance and coping efficacy mediated the relationship between spouses' unsupportive behaviors and patient psychological distress. Perceived control of emotional aspects of the illness, including emotional responses and relationships with family and friends, and perceived control of the medical course of the cancer did not mediate the relationship between spouses' unsupportive behaviors and patient psychological distress. These findings suggest 2 mechanisms to explain why unsupportive responses from spouses may be associated with psychological distress among cancer patients.

Risk factors for poor health-related quality of life in adolescents with epilepsy.

PURPOSE: To examine potential risk factors for poor health-related quality of life (HRQOL) among adolescents with epilepsy by using the newly developed QOLIE-AD-48. Risk factors were derived from sociodemographic, social, academic, and epilepsy- and health-related domains. METHODS: The QOLIE-AD-48 was administered to 197 English-speaking adolescents (age 11-17 years from >20 sites in the United States and in Canada). The self-report instrument yields an overall HRQOL score and eight subscale scores. Other data were obtained from family interviews, physician reports, and health records. Multiple regression analyses were conducted to study risk factors for impairment of HRQOL. RESULTS: Older adolescents (age 14-17 years), those with more severe epilepsy and more symptoms of neurotoxicity, and those living in households with lower socioeconomic status were more likely to report poor overall HRQOL. Risk factors in the eight HRQOL domains were found as follows: (a) Epilepsy Impact: older age in adolescence, more severe epilepsy and neurotoxicity, more hospitalizations during the past year, and fewer hours of extracurricular activities; (b) Memory and Concentration: longer duration of epilepsy, special education classes, and history of repeating a grade in school; (c) Attitude Toward Illness: older age, female gender, and more severe epilepsy and neurotoxicity; (d) Social Support: younger age, male gender, and fewer hospitalizations in the last year; (e) Stigma: lower socioeconomic status and special-education classes; and (f) Health Perceptions: older age, female gender, and lower socioeconomic status. None of the factors examined was significantly associated with HRQOL in (g) Physical Functioning or (h) School Behavior subscales. CONCLUSIONS: We identified several risk factors for poor HRQOL outcomes in adolescents with epilepsy. Age, increased seizure severity, and neurotoxicity were most consistently associated with poor HRQOL across domains. Older adolescents, independent of epilepsy severity, reported worse overall HRQOL than did their younger counterparts. Older adolescents also were more likely to perceive a greater negative impact on life and general health, and had more negative attitudes toward epilepsy. Adolescent boys and girls may show different sensitivities to various quality-of-life domains.

Development of the Quality of Life in Epilepsy Inventory for Adolescents: the QOLIE-AD-48.

PURPOSE: We report the development of an instrument to assess health-related quality of life (HRQOL) in adolescents with epilepsy. METHODS: A sample of 197 English-speaking adolescents (aged 11-17 years) with epilepsy completed a test questionnaire of 88 items. Also included were mastery and self-esteem scales to assess external validity. A parent simultaneously completed an 11-item questionnaire to evaluate the child's HRQOL. Both adolescent and parent questionnaires were repeated in 2-4 weeks. Demographic information and information pertaining to seizures were collected at baseline along with assessment of systemic and neurologic toxicity. RESULTS: The QOLIE-AD-48 contains 48 items in eight subscales: epilepsy impact (12 items), memory/concentration (10), attitudes toward epilepsy (four), physical functioning (five), stigma (six), social support (four), school behavior (four), health perceptions (three), and a total summary score, with higher scores indicating better HRQOL. Internal construct validity was demonstrated in a single-factor solution for the eight dimensions. All correlations were statistically significant at p < 0.05 level. Internal consistency reliability estimated by Cronbach's alpha coefficient was 0.74 for the summary score and ranged from a low of 0.52 (three-item Health Perceptions Scale) to 0.73-0.94 for the other individual scales. Good test-retest reliability was found for the overall measure (0.83). Summary score correlations with the two external validity scales, self-efficacy and self-esteem were 0.65 and 0.54, respectively. Statistically significant differences in summary scores indicating that HRQOL was increasingly better for adolescents as seizure severity decreases (no seizures = 77+/-13, low = 70+/-17, high = 63+/-17) were found among seizure-severity groups. CONCLUSIONS: These data describe the development of a robust instrument to evaluate HRQOL in adolescents with epilepsy. Empiric analyses provide strong evidence that the QOLIE-AD-48 is both a reliable and valid measure for adolescents with epilepsy.

The physical, functional, and developmental outcome of pediatric burn survivors from 1 to 12 months postinjury.

Fifty-one children with an average age of 27 months and who had sustained a burn injury were tested at 1, 6, and 12 months postinjury to determine their physical, functional, and developmental outcomes. Most parents were either African-American or Hispanic, lived on public assistance, and had a high school education or less. Most children had normal range of motion and were appropriate for their age in self-care skills. On the basis of the Home Screening Questionnaire, 48% of the children came from suspect home environments. Developmental delays were noted in language acquisition that persisted over the first year postburn. Although the outcomes of these burn injuries were good in physical and functional areas, the developmental findings raised concerns. The results alert clinicians to screen for potential developmental problems during the burned child's recovery phase and to include appropriate developmental activities and parental guidance in the treatment plan.

The moderating effects of gender and ethnicity on the relationship between effect expectancies and alcohol problems.

OBJECTIVE: Research has demonstrated that alcohol outcome expectancies moderate the relationship between psychological states such as stress and negative affect and alcohol use. This study examined whether the relationship between expectancies and alcohol problems would be moderated by gender and ethnicity. METHOD: Using a household survey format, personal interviews were conducted with Puerto Rican and Irish American men and women. The final sample consisted of 412 (231 male) Puerto Ricans and 476 (252 male) Irish Americans. Alcohol expectancies were measured with the Effects of Drinking Alcohol Scale. All subjects resided in the New York metropolitan area. The original study was designed to compare the drinking behaviors and alcohol-related beliefs of groups with varied drinking practices and distinct drinking beliefs. RESULTS: Both gender and ethnicity moderated the links between aggressive and self-control expectancies and drinking problems. For example, anticipated loss of control from drinking was more negatively related to Puerto Rican and female alcohol problems than it was to Irish and male problems. CONCLUSIONS: The present findings suggest that whether an outcome expectancy is associated with more alcohol problems depends upon the particular meaning of the outcome. This meaning, in turn, depends upon an individual's particular sociocultural perspective which is associated with such personal characteristics as gender and ethnicity.

The relationship between ethnicity, gender and alcohol consumption: a strategy for testing competing models.

AIM: This study tested mediator, moderator and main effects models to determine the pattern of relationships between ethnicity, gender, temperament, and alcohol use. DESIGN: A large-scale survey was employed. Respondents were interviewed in their homes. Participants were 523 Puerto Rican and 490 Irish American adults residing in the New York metropolitan area. MEASURES: Quantity and frequency of alcohol consumption were assessed with standard measures, and recent drinking problems with the substance abuse module of the Composite International Diagnostic Instrument. FINDINGS: Rather than supporting a complex, nested model, the findings supported a main effects model and indicated that each of the three predictors was related to one or more drinking measure. While gender strongly influenced each drinking behavior, ethnicity only influenced frequency, and temperament only influenced recent drinking problems. CONCLUSIONS: The results support previous studies indicating consistent male-female drinking differences while highlighting a statistical strategy for comparing competing models of ethnic drinking behavior.

The origin of life: self-replicating asymmetrical frozen probability.

Within each of us, as within each living or extinct creature, is a broad piece from the story of life and creation. Both the evolution of the universe and the emergence of life on Earth can be considered as being the result of critical events, such as phase transitions, that occur with a certain probability and are characterized by a sudden breakage of prior symmetry. These in turn result in self-perpetuating conditions that are responsible for what we know and perceive today.

Time reversal in biological systems.

Fundamental physical laws provide us appropriate descriptions of the basic behavior of nature. Science possesses a hierarchical structure with various levels of complexity and organization. This extends from the physics of elementary particles and atomic constituents, to the chemistry of molecules, to the biology of the cell and multicellular levels, up to an individual and beyond. Molecular biology thus has its roots based upon fundamental physical descriptors of macromolecules and chemical reactions. The purpose of this paper is to relate an operation in physics, time reversal symmetry, to the realm of biology. This is done with regard to the process of carcinogenesis. Tumor development and progression can be considered a microcosm of evolution, on the level of an individual organism, as well as from the aspect of evolutionary lineage. The driving forces of selection inherent in malignancy can be considered to result in the emergence of a new biological species, which is characterized by reproductive immortality and a remarkable equivalence with our unicellular ancestors. Thus, by its very nature, carcinogenesis as a closed system conceptually represents a reversal of motion with respect to order, stability and evolutionary standards of time.